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J Biol Chem, Vol. 275, Issue 16, 12237-12242, April 21, 2000
From the We have positionally cloned and characterized a
new calcium channel auxiliary subunit,
Functional Properties of a New Voltage-dependent
Calcium Channel
2
Auxiliary Subunit Gene
(CACNA2D2) *
,,,,
,,
Hamon Center for Therapeutic Oncology
Research, Departments of Internal Medicine, Pharmacology, and
§ Physiology, University of Texas, Southwestern Medical
Center, Dallas, Texas 75390, ¶ University of Birmingham,
Birmingham B15 2TT, United Kingdom, Laboratory of Immunobiology,
NCI-Frederick Cancer Research and Development Center, Frederick,
Maryland 21702, and ** Department of Pharmacology, University of
Virginia, Charlottesville, Virginia 22908
2
-2
(CACNA2D2), which shares 56% amino acid identity with the
known 2-1 subunit. The gene maps to the critical
human tumor suppressor gene region in chromosome 3p21.3, showing very
frequent allele loss and occasional homozygous deletions in lung,
breast, and other cancers. The tissue distribution of
2-2 expression is different from
2-1, and 2-2 mRNA is most
abundantly expressed in lung and testis and well expressed in brain,
heart, and pancreas. In contrast, 2-1 is expressed predominantly in brain, heart, and skeletal muscle. When co-expressed (via cRNA injections) with 1B and 
3
subunits in Xenopus oocytes, 2-2
increased peak size of the N-type Ca2+ currents 9-fold, and
when co-expressed with 1C or 1G subunits in Xenopus oocytes increased peak size of L-type channels
2-fold and T-type channels 1.8-fold, respectively. Anti-peptide
antibodies detect the expression of a 129-kDa 2-2
polypeptide in some but not all lung tumor cells. We conclude that the
2-2 gene encodes a functional auxiliary subunit of
voltage-gated Ca2+ channels. Because of its chromosomal
location and expression patterns, CACNA2D2 needs to be
explored as a potential tumor suppressor gene linking Ca2+
signaling and lung, breast, and other cancer pathogenesis. The homologous location on mouse chromosome 9 is also the site of the mouse
neurologic mutant ducky (du), and thus,
CACNA2D2 is also a candidate gene for this inherited
idiopathic generalized epilepsy syndrome.
*
This work was supported by National Institutes of Health
(NCI) Grants CA71618, P50-CA70907, NS38691, and NO1-CO-56000 and by the
Hibino Memorial Medical Fund.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Hamon Center for
Therapeutic Oncology Research, University of Texas Southwestern Medical
Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8593. Tel.:
214-648-4900; Fax: 214-648-4940; E-mail:
minna@simmons.swmed.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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